(1) Field of the Invention
The present invention relates to a method for crystallizing insulin or insulin analogs under alkaline conditions and purifying the insulin or insulin analog crystals by filtering through a filter and drying the insulin or insulin analog crystals captured on the filter to produce crystalline insulin or insulin analog crystal compositions. In particular aspects, the present invention relates to a method for preparing crystals of insulin glargine.
(2) Description of Related Art
Diabetes mellitus is a chronic metabolic disorder caused by either a deficiency of insulin generated by pancreatic beta cells (Type 1) or an acquired cellular resistance to insulin (Type 2). Both Type 1 and Type 2 diabetes result in hyperglycemia, which can in turn result in long term complications. Since the introduction of insulin in 1921, all forms of diabetes have become treatable.
It is well known in the art that insulin may be crystallized in the presence of zinc ions, resulting in a crystalline preparation with significant benefits over amorphous, uncrystallized insulin with regards to stability, storage, formulation, and/or administration. Methods for crystallizing insulin or insulin analogs have been disclosed in U.S. Pat. Nos. 5,952,297; 5,028,587; 5,504,188; 5,952,297 and 7,193,035. Methods for crystallizing an insulin analog in the absence of zinc ions is disclosed in U.S. Pat. No. 7,193,035, which discloses zinc-free crystallization of an insulin analog performed at a pH in the range of about 4.0 to about 7.5. Methods for crystallizing mixed crystals of insulin and insulin derivatives is disclosed in U.S. Pat. No. 5,028,587. Mühlig et al., J. Crystal Growth 232: 93-101 (2001) describe a modified batch crystallization method that was used to prepare crystals of insulin glargine.
While there are methods available for crystallizing insulin and insulin analogs, there is a need in the art for alternative methods of crystallizing insulin or insulin analogs.